Heart failure (HF) refers to a clinical syndrome in which an abnormality of cardiac function causes a below normal cardiac output that can fall below a level adequate to meet the metabolic demand of peripheral tissues. It can be due to a variety of etiologies with ischemic heart disease being the most common. Heart failure is usually treated with a drug regimen designed to augment cardiac function and/or relieve congestive symptoms. It has also been shown that some heart failure patients suffer from intraventricular and/or interventricular conduction defects (e.g., bundle branch blocks) such that their cardiac outputs can be increased by improving the synchronization of ventricular contractions with electrical stimulation. In order to treat these problems, implantable cardiac devices have been developed that provide appropriately timed electrical stimulation to one or more heart chambers in an attempt to improve the coordination of atrial and/or ventricular contractions, termed cardiac resynchronization therapy (CRT).
The treatments for HF discussed above are most appropriately used to treat patients with systolic dysfunction. In such patients, the fraction of the blood accumulated during diastolic filling of one or both ventricles that is pumped out during systole, referred to as the ejection fraction (EF), is below normal. Some HF patients, however, are shown to maintain a normal left ventricular EF. Of the more than 5 million Americans who have heart failure (HF), 30% to 50% have HF with preserved ejection fraction (HF-PEF). HF-PEF is associated with high morbidity and mortality, and HF-PEF commonly occurs in elderly patients with comorbidities of hypertension, left ventricular hypertrophy, diabetes, myocardial ischemia, and obesity. Although the mechanisms of HF with a normal EF are incompletely understood, diastolic dysfunction is a central component, leading to it also being referred to as diastolic heart failure (DHF). Current treatment modalities have improved the prognosis among individuals with HF and a depressed EF but have not been as successful in patients with HF-PEF.